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Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability

Therriault, Joseph ; Janelidze, Shorena LU ; Benedet, Andréa Lessa LU ; Ashton, Nicholas J ; Arranz Martínez, Javier ; Gonzalez-Escalante, Armand ; Bellaver, Bruna ; Alcolea, Daniel ; Vrillon, Agathe and Karim, Helmet , et al. (2024) In Nature Aging 4(11). p.1529-1537
Abstract

Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five... (More)

Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.

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type
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publication status
published
subject
keywords
Alzheimer Disease/blood, Humans, Biomarkers/blood, tau Proteins/blood, Amyloid beta-Peptides/blood, Aged, Female, Male, Cognitive Dysfunction/blood, Middle Aged, Cohort Studies, Positron-Emission Tomography, Predictive Value of Tests, Aged, 80 and over, Probability
in
Nature Aging
volume
4
issue
11
pages
1529 - 1537
publisher
Springer
external identifiers
  • scopus:85208981612
  • pmid:39533113
DOI
10.1038/s43587-024-00731-y
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
7e46bfe2-c550-4015-b831-02073885f790
date added to LUP
2025-01-27 14:49:18
date last changed
2025-06-18 00:47:18
@article{7e46bfe2-c550-4015-b831-02073885f790,
  abstract     = {{<p>Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.</p>}},
  author       = {{Therriault, Joseph and Janelidze, Shorena and Benedet, Andréa Lessa and Ashton, Nicholas J and Arranz Martínez, Javier and Gonzalez-Escalante, Armand and Bellaver, Bruna and Alcolea, Daniel and Vrillon, Agathe and Karim, Helmet and Mielke, Michelle M and Hyung Hong, Chang and Roh, Hyun Woong and Contador, José and Puig Pijoan, Albert and Algeciras-Schimnich, Alicia and Vemuri, Prashanthi and Graff-Radford, Jonathan and Lowe, Val J and Karikari, Thomas K and Jonaitis, Erin and Brum, Wagner and Tissot, Cécile and Servaes, Stijn and Rahmouni, Nesrine and Macedo, Arthur C and Stevenson, Jenna and Fernandez-Arias, Jaime and Wang, Yi-Ting and Woo, Marcel S and Friese, Manuel A and Jia, Wan Lu and Dumurgier, Julien and Hourregue, Claire and Cognat, Emmanuel and Ferreira, Pamela Lukasewicz and Vitali, Paolo and Johnson, Sterling and Pascoal, Tharick A and Gauthier, Serge and Lleó, Alberto and Paquet, Claire and Petersen, Ronald C and Salmon, David and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Stomrud, Erik and Galasko, Douglas and Son, Sang Joon and Zetterberg, Henrik and Fortea, Juan and Suárez-Calvet, Marc and Jack, Clifford R and Blennow, Kaj and Hansson, Oskar and Rosa-Neto, Pedro}},
  keywords     = {{Alzheimer Disease/blood; Humans; Biomarkers/blood; tau Proteins/blood; Amyloid beta-Peptides/blood; Aged; Female; Male; Cognitive Dysfunction/blood; Middle Aged; Cohort Studies; Positron-Emission Tomography; Predictive Value of Tests; Aged, 80 and over; Probability}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1529--1537}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability}},
  url          = {{http://dx.doi.org/10.1038/s43587-024-00731-y}},
  doi          = {{10.1038/s43587-024-00731-y}},
  volume       = {{4}},
  year         = {{2024}},
}